Antigen-specific T Cell Therapy for AML or MDS Patients With Relapsed Disease After Allo-HCT

NCT04284228 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: NEXI-001-01
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 5

Brief Summary

This Research study is being done to characterize the safety, tolerability, and preliminary antitumor activity of the NEXI-001 T cell product (a new experimental therapy), which contains populations of CD8+ T cells targeting multiple leukemia associated antigen peptides in patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) who have relapsed disease after an allogeneic hematopoietic cell transplant (HCT). The study will enroll AML or MDS patients who have either Minimal Residual Disease (MRD) or relapsed disease after a human leukocyte antigen (HLA)-matched allogeneic HCT. Patients who have had an HLA-mismatched or haploidentical allogeneic HCT will not be eligible to participate in this study. Eligible patients for this study must also have ≥ 50% T-cell chimerism from the original donor at the time study entry. The enrolled patients will undergo bridging therapy for the purposes of disease control while the NEXI-001 T cell product is being manufactured. Choice of bridging therapy administered will be per the Investigator's discretion, but is limited to acceptable agents as specified in the protocol. Bridging therapy will be administered prior to lymphodepleting (LD) therapy, with the last dose of the bridging therapy administered ≥ 14 days prior to initiation of LD therapy. Within 72 hours after completing LD therapy, patients will receive a single IV infusion of the NEXI-001 T cell product.

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)

Keywords

AML; MDS; HCT

Outcome Measures

Primary Outcomes (9)

• Adverse Events of Special Interest (AESIs) events

  Dose Limiting Toxicities (DLTs)

  At year 1

• Adverse Events of Special Interest (AESIs) events

  For Incidence of TEAEs and serious TEAEs (Treatment-emergent adverse events (TEAEs) are defined as those AEs that started on or after LD therapy or that worsened after LD therapy

  At year 1

• Adverse Events of Special Interest (AESIs) events (AEs)

  Infusion Related Reactions (IRR)

  At year1

• Survival

  Median Progressive free Survival (PFS)

  At 12 months

• Survival

  Overall Response Rate (ORR)

  At 12 months

• Survival

  Overall Survival (OS)

  At 12 months

• Adverse events (AEs) Reporting

  Incidence of TEAEs leading to study withdrawal

  At year 1

• Adverse Events of Special Interest (AESIs) events (AEs) Reporting

  Cytokine Release Syndrome (CRS)

  At year 1

• Adverse Events of Special Interest (AESIs)events (AEs) Reporting

  Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS)

  At year 1

Study Arms (2)

Safety Evaluation Phase

EXPERIMENTAL

Treatment with NEXI-001 T cells, derived from PBMCs of original HLA- matched HCT donor.

Biological: Infusion of NEXI-001 T Cells

Dose Expansion Phase

EXPERIMENTAL

Dose Expansion Phase to further define the safety, tolerability and initial anti-tumor efficacy of the NEXI-001 T cell product at the dose established from the Safety Evaluation Phase.

Biological: Infusion of NEXI-001 T Cells

Interventions

Infusion of NEXI-001 T Cells BIOLOGICAL

Procedure: A single IV infusion of NEXI-001 T Cells at Day 1 after Lymphodepletion(LD) Therapy. At dose Level 1: 1.0 x 108 total viable T cells At dose Level 2: 2.0 x 108 total viable T cells Procedure: Lymphodepletion: IV administration of fludarabine 30 mg/2 and cyclophosphamide 300 mg/m2 for 3 days. lymphodepletion (LD) Therapy: Subjects will received bridging therapy agents during lymphodepletion for 3 consecutive days prior to receiving the NEXI-001 product Drug: Fludarabine Fludarabine infusion Other Name: Fludarabine monophosphate Drug: Cyclophosphamide Cyclophosphamide infusion Other Name: Cytoxan

Dose Expansion Phase; Safety Evaluation Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• General
• Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that are not part of standard-of-care for the patient's disease. Patients must also be willing and able to comply with study procedures, including the acquisition of specified research specimens
• Age ≥ 18 years old
• Expression of HLA-A\*0201 as determined by high resolution sequence-based typing method (e.g. TruSight HLA v2 Sequence Panel)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients must have a confirmed diagnosis of AML (according to World Health Organization (WHO) classification) or MDS with evidence of MRD or morphological relapse after HLA-matched allogeneic HCT
• MRD includes:
• Detection of blasts \<5% in bone marrow
• Detection of a clonal abnormal blast population via multi-color flow cytometry
• Detection of known or new myeloid gene mutations
• Donor match at 10 of 10 loci for HLA-A, -B, -C, -DRB1 and DQB1, with each typed at high resolution by DNA-based methods.
• a. Patients who have had prior HLA-mismatched or haploidentical allogeneic HCT will not be eligible
• T-cell chimerism ≥ 50% to donor (by PCR analysis)
• Acceptable laboratory parameters as follows:
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN)

You may not qualify if:

• Active acute or chronic graft versus host disease (GvHD)
• Eligible patients will not be on any steroids ≥10 mg per day prednisone or equivalent or other immunosuppressants such as tacrolimus, cyclosporine, etc.
• Intermittent topical, inhaled or intranasal corticosteroids are allowed
• Have active or uncontrolled infections with positive cultures and/or requiring treatment with IV anti-infective agents
• History of clinically significant cardiovascular disease including but not limited to:
• Myocardial infarction or unstable angina within the 6 months prior to the initiation of study
• Stroke or transient ischemic attack within 6 months prior to initiation of study
• Clinically significant cardiac arrhythmia
• Uncontrolled hypertension: systolic blood pressure (SBP) \> 180 mmHg, diastolic blood pressure (DBP) \> 100 mmHg
• Congestive heart failure (New York Heart Association \[NYHA\] class III-IV)
• Pericarditis or clinically significant pericardial effusion
• Myocarditis
• Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation
• History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus erythematosus, etc.) resulting in end organ injury or requiring systemic immunosuppression / systemic disease modifying agents within the last 2 years prior to enrollment. Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and subjects with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible for the study
• Human immunodeficiency virus (HIV) seropositive; HIV testing within 2 years of enrollment

Sponsors & Collaborators

• NexImmune Inc.: lead

Study Sites (5)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Advent Health Medical Group Blood & Marrow Transplant

Orlando, Florida, 32804, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

The James Cancer Hospital and Solove Research Institute OSUCC

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Juan Varela, MD, PhD

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: There are two parts to this study. The initial Safety Evaluation Phase will determine the safety and tolerability of a single dose of NEXI-001 T cells. The second part of the study, the Dose Expansion Phase, to further define the safety and evaluate the initial efficacy of the NEXI-001 T cells at the dose established from the Safety Evaluation Phase.

Study Record Dates

• First Submitted: February 3, 2020
• First Posted: February 25, 2020
• Study Start: February 20, 2020
• Primary Completion: October 1, 2024
• Study Completion: March 1, 2025
• Last Updated: January 16, 2024

Record last verified: 2024-01

Locations

US (5)